The main objective of this proposal is to test the hypothesis that two types of nutritional manipulations (fasting and supplemented fasting) disrupts the homeostasis of the reproductive endocrine system of adult men and women by exerting an effect on one or more key points in the hypothalamic-pituitary axis (i.e. pituitary secretion. gonadotropin metabolism and gonadotropin exretion). Three main approaches will be utilized: 1) studies in human volunteers; 2) validation of a monkey model; 3) initiation of studies with in vitro systems. In the human studies the objectives are: 1) to closely monitor the gonadotropin metabolic pathways during nutritional alterations in postmenopausal, (PMW) cycling women and men. Gonadotropin secretion characteristics will be derived from both studies of endogenous pulsations and the response of the pituitary to exogenous LHRH administered by continuous infusion; 2) to determine whether the degradation and excretion properties of circulating gonadotropins are attributable to the presence of heterogeneous forms within the circulation, (by comparing immunoreactive to bioactive potencies in in vitro bioassays during different nutritional states); 3) to examine the influences of steroid replacement in PMW upon gonadotropin excretion during fasting and refeeding; and 4) to establish the relative safety of the two weight reduction regimens upon the menstrual cycles of young women with immediately preceding ovulatory cycles. The objective of the primate studies is to validate the bonnet monkey (Macaca radiata) as a model for the gonadotropic metabolic alterations occurring as a result of nutritional alterations in the human. The objectives of the in vitro studies are: to determine whether the liver and kidney are important regulators of gonadotropin metabolism. Furthermore, we wish to examine the relative efficiency of the hepatic receptors in kidney to remove desialylated hormones from the circulation (by degradation or renal excretion).